Suicide is a Major Problem: In 2017, in the USA, suicide was the second leading cause of death among individuals between the ages of 10 and 34, with twice as many suicides as there were homicides[1].  Suicide is significantly more prevalent in veterans, in which approximately 20 deaths per day occur[2].

New Approaches are Needed: Psychotherapy and current drug interventions have not significantly reduced the rate of suicide.  In fact, suicide rates have increased approximately 60% since 1981[3]. 

Suicide is not only Mental: Suicidal ideation and suicide have been associated with inborn genetic components[4] as well as various forms of inflammation that occur as a result of brain injury[5].  In some situations, depression or other pathological mental states have been shown to induce inflammation[6], which is subsequently associated with suicidal ideation and suicide[7].

Inflammation is Major Cause of Suicide:  Molecular signals which in healthy individuals are associated with the body fighting disease, such as TNF-alpha, are turned by the brain when they are needed, and turned off when the disease has been defeated.  In patients with suicidal ideation, these signals are turned on at a low level without being turned off.  It is known that these “inflammatory signals”, otherwise known as “inflammatory cytokines” are associated with depression based human studies in which inflammatory signals were artificially manufactured and administered in patients to fight cancer and treated patients became depressed[8].  Additionally, studies show that patients who are successfully treated for depression have a reduction in inflammatory signals in the blood[9][10].  Furthermore, various cofactors known to increase suicide rates such as drug abuse[11], alcoholism[12], and brain injury[13], have been shown to increase inflammatory signaling.

Diagnosis

  1. Analysis of what is happening in blood. Proprietary algorithm utilizing already available blood tests to establish patients at risk of suicide (Doctor or rehab facility sends to us lab results from Quest and we plug into our computer and give risk score)
  2. Analysis of what is happening in brain. Brain produces very small particles called exosomes that we can isolate, and they tell us how much inflammation is happening specifically in brain. Additionally, when appropriate, imaging studies using fMRI and various dyes to detect specific areas of brain atrophy and/or inflammation
  3. Analysis of what is happening in the gut. Analysis of the microbiome in gut suggests overall inflammation in body
  4. Analysis of suicide associated gene. Several gene polymorphisms have been shown to be associated with suicide.

The above physical findings are utilized to develop a suicide risk score, as well as to establish a baseline for intervention.  In some situations physicians will only be interested in attaining our suicide risk score and they will perform their own interventions. We are the only group to have developed a suicide risk score based on medical and not psychological findings.

Intervention

  1. Clinical trial of QuadraMune™, clinically validated to reduces biomarkers associated with suicide risk
  2. Broad acting anti-inflammatory natural interventions. Intravenous vitamin C, vitamin D, fish oil, quercetin, micronutrients.
  3. Specific anti-inflammatory antibodies. Anti-TNF, anti-IL-17, anti-IL21
  4. Microbiome modulators. Probiotics, prebiotics, fecal transplants
  5. Cell based therapies. Autologous bone marrow
  6. Transcranial Magnetic Stimulation. Various studies have shown ability to reduce neural inflammation and augment brain regeneration using this approach.

Action Plan

  1. Understanding intellectual property landscape around our broad ideas of diagnosis and treatment. Filing new patents and/or licensing.
  2. Creation of a “Central Core” which analyzes data and provides patient specific recommendations together with the input from the health care professional
  3. Collaboration with medical professionals, drug rehab clinics, etc

     

    Resources
    [1] https://www.nimh.nih.gov/health/statistics/suicide.shtml#part_154968
    [2] https://www.mentalhealth.va.gov/docs/2016suicidedatareport.pdf
    [3] https://webappa.cdc.gov/sasweb/ncipc/mortrate.html
    [4] https://www.sciencedaily.com/releases/2011/10/111007113941.htm
    [5] Juengst et al. Exploratory associations with tumor necrosis factor-α, disinhibition and suicidal endorsement after traumatic brain injury. Brain Behav Immun. 2014 Oct;41:134-43. 
    [6] Zhu et al. Neuroinflammation caused by mental stress: the effect of chronic restraint stress and acute repeated social defeat stress in mice. Neurol Res. 2019 Aug;41(8):762-769
    [7] O’Donovan et al. Suicidal ideation is associated with elevated inflammation in patients with major depressive disorder. Depress Anxiety. 2013 Apr;30(4):307-14.
    [8] Illman et al. Are inflammatory cytokines the common link between cancer-associated cachexia and depression? J Support Oncol. 2005 Jan-Feb;3(1):37-50.
    [9] Lanquillon et al. Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology. 2000 Apr;22(4):370-9.
    [10] Chen et al. Rapid inflammation modulation and antidepressant efficacy of a low-dose ketamine infusion in treatment-resistant depression: A randomized, double-blind control study. Psychiatry Res. 2018 Nov;269:207-211.
    [11] Kapasi et al. Morphine stimulates mesangial cell TNF-alpha and nitrite production. Inflammation. 2000 Oct;24(5):463-76.
    [12] Valles et al. Chronic ethanol treatment enhances inflammatory mediators and cell death in the brain and in astrocytes. Brain Pathol. 2004;14:365–371.
    [13] Yang et al. Serum macrophage migration inhibitory factor concentrations correlate with prognosis of traumatic brain injury. Clin Chim Acta. 2017 Jun;469:99-104.